Interleukin-1 polymorphisms associated with increased risk of gastric cancer

Helicobacter pylori infection is associated with a variety of clinical outc omes including gastric cancer and duodenal ulcer disease(1). The reasons fo r this variation are not clear, but the gastric physiological response is i nfluenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to t he antrum retain normal (or even high) acid secretion(2), whereas individua ls with extensive corpus gastritis develop hypochlorhydria and gastric atro phy(3), which are presumptive precursors of gastric cancer(4). Here we repo rt that interleukin-1 gene cluster polymorphisms suspected of enhancing pro duction of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these poly morphism are hi near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro. The a ssociation with disease may be explained by the biological properties of in terleukin-1-beta, which is an important pro-inflammatory cytokine(5) and a powerful inhibitor of gastric acid secretion(6,7). Host genetic factors tha t affect interleukin-1-beta may determine why some individuals infected wit h H. pylori develop gastric cancer while others do not.